The goals of this project are to define the immunologic mechanisms responsible for resistance to filarial infection, acquisition of filarial disease, and the pathological reactions that develop in patients being treated for these infections. From observations from an island population 17 years apart, individuals were seen to remain entirely free from infection with bancroftian filariasis, their landing greater certainty to classifying them as "putatively immune." Their serologic, lymphocyte proliferation, and PBMC cytokine responses to adult worms and microfilarial antigen were significantly greater than those of infected individuals. Analysis of possible protective immune responses to infective larval antigens is underway. The development of overt lymphatic pathology in patients followed for 17 years did not correlate with either clearance of microfilaremia or enhanced immune responsiveness to parasite antigens. Predisposition to infection might relate to prenatal tolerization to microfilarial antigen identified in children 17 years after their mothers were diagnosed as being either microfilaremic or non-infected during pregnancy. Mechanisms of this immunological tolerance and genetic factors relating to immune and pathological responses are being explored. The acute post-treatment inflammatory responses to DEC treatment of bancroftian filariasis and onchocerciasis have been shown to be related to serum levels of IL-6 and TNF. Similar detailed studies have been carried out on onchocerciasis patients being treated with ivermectin, and evaluation of the specimens is underway.